Nicotine & Tobacco Research, Volume 13, Number 6 (June 2011) 492–497
Brief Report
Effect of Stress and Bupropion on Craving, Withdrawal Symptoms, and Mood in Smokers Michael Kotlyar, Pharm.D.,1,2 David Drone , MHA,3 Paul Thuras, Ph.D.,2 Dorothy K. Hatsukami, Ph.D.,2,4 Lisa Brauer, Ph.D.,2 David E. Adson, M.D.,2 & Mustafa al’Absi, Ph.D.5,6,7 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN Department of Psychiatry, University of Minnesota, Minneapolis, MN 3 University of Minnesota College of Pharmacy, Minneapolis, MN 4 University of Minnesota Tobacco Research Programs, Minneapolis, MN 5 Department of Behavioral Sciences, University of Minnesota Medical School, Duluth, MN 6 Department of Family Medicine, University of Minnesota Medical School, Duluth, MN 7 Department of Physiology, University of Minnesota Medical School, Duluth, MN 1 2
Corresponding Author: Michael Kotlyar, Pharm.D., Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 7-170 Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA. Telephone: 612-625-1160; Fax: 612-625-3927; E-mail:
[email protected] Received August 20, 2010; accepted January 10, 2011
Abstract Introduction: Studies suggest that in smokers attempting to quit smoking, the occurrence of stressful events is associated with smoking relapse. The purpose of this study was to determine the effect of bupropion (an agent known to increase smoking cessation rates) on the craving, withdrawal, and mood response to stressful tasks administered in a laboratory setting. Methods: Response to three tasks (a speech, math, and cold pressor task) was measured in 65 smokers during ad libitum smoking. Smokers were then randomized to either bupropion or placebo. Fourteen days after starting medication, 43 subjects (28 receiving bupropion and 15 receiving placebo) quit smoking and laboratory procedures were repeated on the third day of abstinence. Results: Prior to cessation, stressors presented in a laboratory setting increased craving, nicotine withdrawal symptoms, and subjective distress but decreased positive affect. Thirty minutes of relaxation after the stressors did not result in these measures returning to prestress levels. During the nicotine withdrawal period, stress-induced responses were generally smaller than during the precessation period. Bupropion (relative to placebo) reduced overall levels of craving and withdrawal symptoms but did not have significant effects on response to stress during the nicotine withdrawal period. Conclusions: This study demonstrates that stress results in sustained increases in craving and withdrawal symptoms and changes in mood symptoms and that bupropion affects overall levels of these symptoms. Further research is needed to determine if modifying response to stress is predictive of an effective treatment for facilitating smoking cessation.
Introduction Exposure to stressful situations is a commonly cited smoking trigger with approximately 40%–50% of smokers indicating that during a smoking cessation attempt, stress contributed to a smoking lapse (Borland, 1990; Cummings, Jaen, & Giovino, 1985; Shiffman, Paty, Gnys, Kassel, & Hickcox, 1996; Swan et al., 1988). Consistent with this, laboratory studies have found that stress increases craving and withdrawal symptoms and affects measures of smoking topography such as the number of cigarettes smoked and inhalation length per puff (al’Absi, Wittmers, Erickson, Hatsukami, & Crouse, 2003; Cherek, 1985; Niaura, Shadel, Britt, & Abrams, 2002; Perkins & Grobe, 1992; Pomerleau & Pomerleau, 1987; Rose, Ananda, & Jarvik, 1983). Medications known to increase smoking cessation rates (e.g., nicotine replacement therapy, bupropion, varenicline) have been shown to decrease craving and withdrawal symptoms during a smoking cessation attempt (Mooney & Sofuoglu, 2006; Shiffman, Ferguson, Gwaltney, Balabanis, & Shadel, 2006; West, Baker, Cappelleri, & Bushmakin, 2008), but there is little data regarding their effect on stress-induced changes in craving and withdrawal symptoms. Since stress is consistently cited as an important precipitant to smoking, it is important to determine if effective medications increase cessation rates (at least in part) by altering how smokers respond to stress. Determining mechanisms by which current medications are effective can lead to better methods to identify and test promising new smoking cessation therapies. The objective of this study is to determine how bupropion affects stress-induced changes in craving, withdrawal, and mood symptoms.
doi: 10.1093/ntr/ntr011 Advance Access published on March 4, 2011 © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail:
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Nicotine & Tobacco Research, Volume 13, Number 6 (June 2011)
Methods Study Design Tobacco craving, withdrawal symptoms, and mood were assessed at each of two laboratory sessions at five timepoints (i.e., prior to an initial 30-min relaxation period, immediately following a speech task, a mental arithmetic task, a cold pressor, and following a final 30-min relaxation period). Thirty minutes separated the three tasks. Prior to the first session, smokers could smoke ad libitum (however, they could not smoke after arrival at the laboratory session). Subjects were then randomized to receive either bupropion, bupropion with behavioral counseling, or matching placebo. Subjects quit smoking after 14 days of medications, and the second laboratory session occurred on the morning of the third day of cessation. Only subjects who abstained from smoking for the required time period (as verified by exhaled CO concentrations
